Professor Andy Clark PhD

Andy Clark

Institute of Inflammation and Ageing
Deputy Institute Director
Joint Institute Lead for Postgraduate Research
Professor of Inflammation Biology

Contact details

Address
Institute of Inflammation and Ageing
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Andy Clark is Professor of Inflammation Biology in the Institute of Inflammation and Ageing. He is a molecular biologist with a long-standing interest in how expression of inflammatory mediators is switched off, contributing to the resolution of inflammation. He is also interested in mechanisms of action of endogenous anti-inflammatory lipids, cytokines and steroid hormones. Andy has received major funding from the Wellcome Trust, MRC and Arthritis Research UK. He has published more than 70 articles and book chapters, many of which have been cited several hundred times.

ORCID ID: 0000-0003-4996-8322

Qualifications

  • PhD, Department of Medicine, University of Birmingham (1992)
  • BA (Hons) Natural Sciences (Genetics), University of Cambridge, UK (1987)

Biography

Andy Clark studied Natural Sciences at the University of Cambridge before doing a PhD in transcriptional regulation of insulin genes at the University of Birmingham. He continued his research at the University of Birmingham for two years, funded by a fellowship from Diabetes UK, before moving to the Cancer Research UK labs in Lincoln’s Inn Fields for three years.

He then worked for almost sixteen years at the Kennedy Institute of Rheumatology, Imperial College London, first as a lecturer, then senior lecturer, then reader. In 2012 Andy was appointed as Professor of Inflammation Biology at the University of Birmingham.

Teaching

  • Immunology and Immunotherapy MSc - Module lead for Inflammation and Cell Migration
  • Biomedical Science BSc - three lectures in “Cellular Pathology” and “Rheumatology and Orthopaedics” modules

Postgraduate supervision

  • Andy supervises laboratory-based research projects for the MSc in Immunology and Immunotherapy
  • Andy has supervised thirteen PhD students to award of degree. Most of these students are still in medical or scientific careers, some in industry, others in academia

Andy is interested in supervising doctoral research students in the following areas:

  • Transcriptional and post-transcriptional gene regulation in the inflammatory response
  • The biology of macrophages in the rheumatoid synovium
  • Anti-inflammatory mechanisms of action of glucocorticoids and interleukin 10

If you are interesting in studying any of these subject areas please contact Professor Andy Clark directly, or for any general doctoral research enquiries, please email mds-gradschool@contacts.bham.ac.uk.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

Research themes

Inflammation, Resolution, Rheumatology, Gene expression.

Research activity

Control of mRNA stability

Inflammatory mediators such as tumour necrosis factor a (TNFa) are potentially harmful. Their expression is tightly regulated and normally occurs in a transient manner, with rapid induction by a pro-inflammatory stimulus followed by a rapid return to baseline. This pattern of gene expression is dependent on dynamic regulation of mRNA stability. We have characterised a phosphorylation-mediated switch that controls the stability of TNFa and many other pro-inflammatory mRNAs. We recently showed that this switch can be targeted to prevent different forms of experimentally-induced inflammatory pathology. Translational implications of these discoveries are being explored.

Feedback nodes

Resolution of inflammation is partly dependent on negative feedback loops, which ensure that responses to pro-inflammatory stimuli are both transient and proportional. For example, pro-inflammatory stimuli activate the MAPK p38 signalling pathway, promoting expression of inflammatory mediators such as TNFa At the same time, the expression of Dual Specificity Phosphatase 1 (DUSP1) is induced. DUSP1 inactivates p38 to terminate the inflammatory response. Negative feedback mechanisms such as this can also be exploited by anti-inflammatory agonists. For example, the expression of DUSP1 is enhanced and extended by anti-inflammatory glucocorticoids, and this results in more rapid and effective inactivation of inflammatory mediator gene expression. We refer to genes that behave like DUSP1 as “Feedback Node Genes”. Their cooperative regulation by both pro- and anti-inflammatory stimuli is poorly understood, but seems to play a major role in limiting inflammation and preventing chronic inflammatory pathology. We are investigating various Feedback Node Genes and trying to understand the basis of their cooperative regulation.

Other activities

  • Member of the Population and Systems Biology Board of the Medical Research Council
  • Member of the Editorial Board of the Journal of Biological Chemistry
  • Member of the Science Committee of the Society for Endocrinology

Publications

Recent publications

Article

O’Neil, JD, Bolimowska, OO, Clayton, SA, Tang, T, Daley, KK, Lara-Reyna, S, Warner, J, Martin, CS, Mahida, RY, Hardy, RS, Arthur, JSC & Clark, AR 2023, 'Dexamethasone impairs the expression of antimicrobial mediators in lipopolysaccharide-activated primary macrophages by inhibiting both expression and function of interferon β', Frontiers in immunology, vol. 14, 1190261. https://doi.org/10.3389/fimmu.2023.1190261

Pucino, V, Nefla, M, Gauthier, V, Alsaleh, G, Clayton, SA, Marshall, J, Filer, A, Clark, AR, Raza, K & Buckley, CD 2023, 'Differential effect of lactate on synovial fibroblast and macrophage effector functions', Frontiers in immunology, vol. 14, 1183825. https://doi.org/10.3389/fimmu.2023.1183825

Clayton, SA, Lockwood, C, O’neil, JD, Daley, KK, Hain, S, Abdelmottaleb, D, Bolimowska, OO, Tennant, DA & Clark, AR 2023, 'The glucocorticoid dexamethasone inhibits HIF-1α stabilization and metabolic reprogramming in lipopolysaccharide-stimulated primary macrophages', Discovery Immunology, vol. 2, no. 1, kyad027, pp. 1-13. https://doi.org/10.1093/discim/kyad027

Clayton, SA, Daley, KK, Macdonald, L, Fernandez-vizarra, E, Bottegoni, G, O’Neil, JD, Major, T, Griffin, D, Zhuang, Q, Adewoye, AB, Woolcock, K, Jones, SW, Goodyear, C, Elmesmari, A, Filer, A, Tennant, DA, Alivernini, S, Buckley, CD, Pitceathly, RDS, Kurowska-stolarska, M & Clark, AR 2021, 'Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifunctional gene C15orf48', Science Advances, vol. 7, no. 50, eabl5182. https://doi.org/10.1126/sciadv.abl5182

Falconer, J, Pucino, V, Clayton, S, Marshall, J, Raizada, S, Adams, H, Philp, A, Clark, AR, Filer, A, Raza, K, Young, S & Buckley, C 2021, 'Spontaneously resolving joint inflammation is characterised by metabolic agility of fibroblast-like synoviocytes', Frontiers in immunology, vol. 12, 725641. https://doi.org/10.3389/fimmu.2021.725641

Alivernini, S, MacDonald, L, Elmesmari, A, Finlay, S, Tolusso, B, Gigante, MR, Petricca, L, Di Mario, C, Bui, L, Perniola, S, Attar, M, Gessi, M, Fedele, AL, Chilaka, S, Somma, D, Sansom, SN, Filer, A, McSharry, C, Millar, NL, Kirschner, K, Nerviani, A, Lewis, MJ, Pitzalis, C, Clark, AR, Ferraccioli, G, Udalova, I, Buckley, C, Gremese, E, McInnes, IB, Otto, TD & Kurowska-Stolarska, M 2020, 'Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis', Nature Medicine, vol. 26, no. 8, pp. 1295-1306. https://doi.org/10.1038/s41591-020-0939-8

Clark, A 2019, 'Enhancing tristetraprolin activity reduces the severity of cigarette smoke-induced experimental chronic obstructive pulmonary disease.', Clinical and Translational Immunology. https://doi.org/10.1002/cti2.1084

Clark, AR & Ohlmeyer, M 2019, 'Protein phosphatase 2A as a therapeutic target in inflammation and neurodegeneration', Pharmacology & Therapeutics, vol. 201, pp. 181-201. https://doi.org/10.1016/j.pharmthera.2019.05.016

Ronkina, N, Shushakova, N, Tiedje, C, Yakovleva, T, Tollenaere, MAX, Scott, A, Batth, TS, Olsen, JV, Helmke, A, Bekker-jensen, SH, Clark, AR, Kotlyarov, A & Gaestel, M 2019, 'The role of TTP phosphorylation in the regulation of inflammatory cytokine production by MK2/3', Journal of Immunology, vol. 203, no. 8, pp. 2291-2300. https://doi.org/10.4049/jimmunol.1801221

Brown, JM, Ross, E, Desanti, G, Saghir, A, Clark, A, Buckley, C, Filer, A, Naylor, A & Claridge, E 2017, 'Detection and characterisation of bone destruction in murine rheumatoid arthritis using statistical shape models', Medical Image Analysis, vol. 40, pp. 30-43. https://doi.org/10.1016/j.media.2017.05.006

Abstract

Barney, K, Hagel, V, Clarke, J, Clark, AR, Abdelmottaleb, D, Raza, K, Anderson, A, Wraith, D & Scheel-Toellner, D 2023, 'Generation of a B Cell Model to Investigate the Function of FcRL4 in the Context of RA', British Society for Immunology Congress 2023, Belfast, United Kingdom, 4/12/23 - 7/12/23.

Review article

Clayton, SA, MacDonald, L, Kurowska-Stolarska, M & Clark, AR 2021, 'Mitochondria as key players in the pathogenesis and treatment of rheumatoid arthritis', Frontiers in immunology, vol. 12, 673916. https://doi.org/10.3389/fimmu.2021.673916

Crowley, T, Buckley, C & Clark, A 2018, 'Stroma: the forgotten cells of innate immune memory', Clinical & Experimental Immunology, vol. 193, no. 1, pp. 24-36. https://doi.org/10.1111/cei.13149

Falconer, J, Young, S, Clark, A & Buckley, C 2018, 'Synovial cell metabolism and chronic inflammation in rheumatoid arthritis', Arthritis and Rheumatology, vol. 70, no. 7, pp. 984-999. https://doi.org/10.1002/art.40504

Clayton, SA, Jones, SW, Kurowska-stolarska, M & Clark, AR 2018, 'The role of microRNAs in glucocorticoid action', Journal of Biological Chemistry, vol. 293, no. 6, pp. 1865-1874. https://doi.org/10.1074/jbc.R117.000366

View all publications in research portal